The 3-amino-substituted glycosylated bile acid derivatives are disclosed in International Publication No. WO 93/11772. These and their related compounds are described as permeation enhancers; that is, these compounds enhance the ability of therapeutically significant compounds to penetrate biological or synthetic membranes. This property of permeation enhancement is observed whether the therapeutically significant compound is combined with the permeation enhancer as an admixture or as a conjugate therewith.
Hence, from a commercial point of view, an efficient synthetic scheme for the preparation of such permeation enhancers, particularly the 3-amino-substituted glycosylated bile acid derivatives, would be extremely attractive.
It should further be pointed out that the commercial attractiveness of a large-scale manufacturing process of 3-amino-substituted glycosylated bile acids (and many of their derivatives) would be enhanced by an abundant supply of phenyl 2,3,4,6-tetrabenzylthioglucose, the preferred initial protected form of the sugar moiety used in the glycosylation of the bile acids and their derivatives.
Earlier efforts were directed toward the one-step conversion of commercially available 2,3,4,6-tetra-O-benzyl-D-glucopyranose to the phenyl 2,3,4,6-tetrabenzylthioglucose compound via treatment with tri-n-butylphosphine/diphenyldisulfide (in 46% yield). These starting materials and/or reagents are quite costly. The tetrabenzylglucopyranose alone is priced at ca. $7,000/kg.
Accordingly, a more economical method of preparing the desired phenyl tetrabenzylthioglucose would, likewise, be a welcome advance.